Regulation by non-major histocompatibility complex genes of the allo-4-hydroxy-phenylpyruvate dioxygenase (F liver protein) response.

Although rapid progress is being made in the quantitative genetics of multifactorial disease, no response to a simple antigen has yet been subjected to full genomic analysis. The well-characterized antigen allo-HPPD (4-hydroxy-phenylpyruvate dioxygenase, previously known as F liver antigen) is a good candidate for such treatment. Old and new data bearing on this possibility are here assembled. In respect of antibody production and an early burst of interleukin-4 (IL-4) transcription, introduction of the non-major histocompatibility complex (MHC) background from A/J strain mice into F1 hybrids with C57BL10 strains up-regulates the response. These findings can be aligned with previous quantitative genetics carried out on airway hyper-responsiveness in related strains, and to a lesser extent with the genetics of autoimmune diabetes in the mouse. Taken together, the findings suggest that regulation of the pro-inflammatory cytokines are largely responsible for the variation. Additional data indicate that these non-MHC genes are are to a variable extent (depending on the response parameter) epistatic to the down-regulatory MHC allele H-2Ab.